A Study of the Combination of Ibrutinib Plus Venetoclax Versus Chlorambucil Plus Obinutuzumab for the First-line Treatment of Participants With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) (GLOW)

Janssen (J&J Innovative Medicine)

Status and phase: Active, not recruiting; Phase 3

Conditions: Leukemia, Lymphocytic, Chronic, B-Cell

Treatments: Drug: Obinutuzumab; Drug: Venetoclax; Drug: Chlorambucil; Drug: Ibrutinib (as Subsequent Therapy); Drug: Ibrutinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT03462719

54179060CLL3011 (Other Identifier)

CR108428

2017-004699-77 (EudraCT Number)

Details and patient eligibility

About

The purpose of this study is to assess progression-free survival (PFS) from treatment with ibrutinib plus venetoclax (I+VEN) compared with obinutuzumab plus chlorambucil (G-Clb) as assessed by an Independent Review Committee (IRC).

Enrollment: 211 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adult participants who are: (a) greater than or equal to (>=) 65 years old or, (b) 18 to 64 years old and have at least 1 of the following:

  1. Cumulative Illness Rating Scale (CIRS) score > 6
  2. Creatinine clearance (CrCl) estimated less than (<) 70 milliliter per minute (mL/min) using Cockcroft-Gault equation

• Diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) that meets International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria

• Measurable nodal disease (by computed tomography [CT]), defined as at least one lymph node > 1.5 centimeter (cm) in longest diameter

• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Grade less than or equal to (<=) 2

• Active CLL/SLL requiring treatment per the iwCLL criteria

Exclusion criteria

• Prior anti-leukemic therapy for CLL or SLL
• Presence of deletion of the short arm of chromosome 17 (del17p) or known TP53 mutation detected at a threshold of >10 percent (%) variable allele frequency (VAF)
• Major surgery within 4 weeks of first dose of study treatment
• Known bleeding disorders (example, von Willebrand's disease or hemophilia)
• Central nervous system (CNS) involvement or suspected Richter's syndrome

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

211 participants in 2 patient groups

Treatment Arm A: Ibrutinib and Venetoclax (I+VEN)

Experimental group

Description:

Participants will initially receive ibrutinib (420 mg \[milligrams\]/day) for 3 cycles. Venetoclax dose ramp up (from 20 to 400 mg over 5 weeks) will begin at Cycle 4 and the combination of ibrutinib and venetoclax will be given for 12 cycles (each cycle is equivalent to 28 days). Participants who subsequently develop progressive disease may enter to Subsequent Therapy Phase to receive single-agent ibrutinib until disease progression or unacceptable toxicity.

Treatment:

Drug: Ibrutinib

Drug: Ibrutinib (as Subsequent Therapy)

Drug: Venetoclax

Treatment Arm B: Chlorambucil and Obinutuzumab (G-Clb)

Active Comparator group

Description:

Participants will receive chlorambucil and obinutuzumab (G-Clb) for 6 cycles. Participants will receive obinutuzumab, 1000 mg intravenously (IV) on Days 1, 8 and 15 of Cycle 1, and on Day 1 of Cycles 2 to 6 and chlorambucil 0.5 milligrams per kilogram (mg/kg) body weight, on Days 1 and 15 of Cycles 1 to 6. Participants who subsequently develop progressive disease may enter to Subsequent Therapy Phase to receive single-agent ibrutinib until disease progression or unacceptable toxicity.

Treatment:

Drug: Ibrutinib (as Subsequent Therapy)

Drug: Chlorambucil

Drug: Obinutuzumab